Irritable bowel syndrome: Relations with functional, mental, and somatoform disorders

This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of “interface disorders” to abandon the dualistic classification of purely organic or purely mental disorders.

Investigation of the effect of military stress on the prevalence of functional bowel disorders

AIM: To investigate the morbidity of functional bowel disorders (FBD) under military stress conditions in order to lay foundations for the prevention and treatment of this disease. METHODS: Four hundred and fifty-seven soldiers who were assigned to specified services and 471 soldiers who were assigned to routine services were enrolled using cluster sampling, with the latter as a control group. They were surveyed using the Rome Ⅲ FBD standard questionnaire. The FBD symptom question-naire included FBD-related symptoms, severity, dura- tion or attack time, and accompanying symptoms. RESULTS: The morbidity of the military stress group (14.6%) was significantly higher than in the control group (9.98%) ( 2 = 4.585, P < 0.05). The incidence of smoking, abdominal pain and acid regurgitation ( 2 = 4.761, P < 0.05) as well as the ZUNG anxiety/depression scores ( 2 = 7.982, P < 0.01) were also sig- nificantly higher in the military stress group compared with the control group. ZUNG anxiety ( 2 = 11.523, P < 0.01) and depression ( 2 = 5.149, P < 0.05) scores were higher in the FBD group compared with the non-FBD group. The differences in the ZUNG self-rated anxiety and depression scales between the 2 groups were statistically significant ( 2 = 14.482, P < 0.01 and 2 = 6.176, P < 0.05). CONCLUSION: The morbidity of FBD was higher under military stress conditions.

Functional gastrointestinal disorders in inflammatory bowel disease: Time for a paradigm shift?

Recent advances in biological therapies have revolutionalised and redefined treatment targets in inflammatory bowel disease(IBD).There is now a stronger emphasis on achieving the more stringent therapeutic goals of mucosal and histological healing,rather than clinical remission alone.Consequently,the treatment of refractory“functional”gastrointestinal symptoms,often attributed as the aftermath of previous inflammation,has recently become more prominent in quiescent disease.With further expected advances in anti-inflammatory treatments on the horizon,the burden of such symptoms in quiescent disease,which have been relatively neglected,is set to become an even bigger problem.In this article,we highlight the current state of research and understanding in this field,including recent developments and clinical practice guidelines on the diagnosis and management of functional gastrointestinal symptoms,such as irritable bowel syndrome and functional anorectal and pelvic floor disorders,in patients with quiescent IBD.These disorders are not only highly prevalent in these patients,they are often misdiagnosed,and are difficult to treat,with very few evidence-based therapies.Moreover,they are associated with substantial impairment in quality-of-life,considerable morbidity,and psychological distress.There is therefore an urgent need for a change in emphasis towards earlier recognition,positive diagnosis,and targeted treatment for patients with ongoing functional gastrointestinal symptoms in the absence of active IBD.This article also highlights the need for further research to develop much needed evidence-based therapies.

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.

Contribution of ghrelin to functional gastrointestinal disorders' pathogenesis

Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.

Bloating and functional gastro-intestinal disorders: Where are we and where are we going?

Bloating is one of the most common and bothersome symptoms complained by a large proportion of patients. This symptom has been described with various definitions, such as sensation of a distended abdomen or an abdominal tension or even excessive gas in the abdomen, although bloating should probably be defined as the feeling (e.g. a subjective sensation) of increased pressure within the abdomen. It is usually associated with functional gastrointestinal disorders, like irritable bowel syndrome, but when bloating is not part of another functional bowel or gastrointestinal disorder it is included as an independent entity in Rome III criteria named functional bloating. In terms of diagnosis, major difficulties are due to the lack of measurable parameters to assess and grade this symptom. In addition, it is still unclear to what extent the individual patient complaint of subjective bloating correlates with the objective evidence of abdominal distension. In fact, despite its clinical, social and economic relevance, bloating lacks a clear pathophysiology explanation, and an effective management endorsement, turning this common symptom into a true challenge for both patients and clinicians. Different theories on bloating etiology call into questions an increased luminal contents (gas, stools, liquid or fat) and/or an impaired abdominal empting and/or an altered intra-abdominal volume displacement (abdomino-phrenic theory) and/or an increased perception of intestinal stimuli with a subsequent use of empirical treatments (diet modifications, antibiotics and/or probiotics, prokinetic drugs, antispasmodics, gas reducing agents and tricyclic antidepressants). In this review, our aim was to review the latest knowledge on bloating physiopathology and therapeutic options trying to shed lights on those processes where a clinician could intervene to modify disease course.

Five-year follow-up of 263 cases of functional bowel disorder

AIM: To determine the mortality associated with functional bowel disorders (FBDs) and their possible relationship with organic bowel disease. METHODS: Patients who satisfied the Rome Ⅲ criteria for FBD (retrospective diagnosis) were followed up by telephone interview and/or outpatient review at 5 years after their first attendance. The patients were divided into the following groups: irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea and unspecified FBD. The survival of the FBD patients overall and of those with each FBD were compared with data obtained from the Guangzhou population in 2005. The incidences of colonic cancer overall and for each FBD were compared with data from the Chinese population obtained from 56 cancer registries in 19 provinces of the country in 2008. RESULTS: Two hundred and sixty-three patients were followed-up. Five patients died, which was not significantly different from the expected survival rate. No differences in mortality among the FBDs were found. There were nine cases of organic bowel disease: three colonic cancers and six colonic polyps. The incidence of colonic cancer in FBD patients was higher than that in the general Chinese population (0.23% vs 0.03%, P < 0.05). There were significant differences in the incidence of colonic cancer among the FBDs (0/134, 0/24, 2/29, 1/66, 0/10, respectively, P<0.05); functional constipation was the most common. The incidence of colonic polyps was similar among the FBDs. The baseline age of patients who died was greater than that of those who survived (66.60±6.84 years vs 45.14±10.34 years, P<0.05). The baseline age of patients who had colonic cancer or polyps during follow-up was greater than that of those without colonic cancer or polyps (60.33±1.53 years vs 45.38±10.62 years; 54.50±6.47 years vs 45.34±10.68 years, P<0.05). CONCLUSION: FBDs do not increase the risk of death. The incidence of colonic cancer in patients with FBDs may be increased, especially in those with functional constipation and in the elderly.

Differential diagnosis between functional and organic intestinal disorders:Is there a role for non-invasive tests?

Abdominal pain and bowel habits alterations are common symptoms in the general population. The investigation to differentiate organic from functional bowel disorders represents a considerable burden both for patients and public health service. The selection of patients who should undergo endoscopic and/or radiological procedures is one of the key points of the diagnostic process, which should avoid the abuse of invasive and expensive tests as well as the underestimation of potentially harmful diseases. Over the cominci years,dinidans and researchers will be challenged to develop strategies to increase the patient＇s compliance and to reduce the economic and social costs of the intestinal diseases.

Patients with functional bowel disorder have disaccharidase deficiency:A single-center study from Russia

BACKGROUND Functional bowel disorder(FBD)may be caused by a decrease in disaccharidase activity.Thus,the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.AIM To determine the potential value of intestinal disaccharidases glucoamylase,maltase,sucrase,and lactase in understanding the etiology and pathogenesis of FBD.METHODS A total of 82 FBD patients were examined.According to the Rome IV criteria(2016),23 patients had diarrhea-predominant irritable bowel syndrome(IBS),33 had functional diarrhea,10 had constipation-predominant IBS,4 had functional constipation,and 12 had mixed IBS.The Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine,in duodenal biopsies obtained during esophagogastroduodenoscopy.RESULTS Lactase deficiency was detected in 86.5%of patients,maltase deficiency in 48.7%,sucrase deficiency in 50%,and glucoamylase deficiency in 84.1%.The activities of all enzymes were reduced in 31.7%of patients,and carbohydrase deficiency was detected in 63.5%of patients.The low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2%of patients.CONCLUSION In 78 of the 82 patients with FBD,gastrointestinal symptoms were associated with disaccharidase deficiency.

Utility of gastrointestinal ultrasound in functional gastrointestinal disorders:A narrative review

Gastrointestinal(GI)ultrasound(GIUS)is valuable in the evaluation of GI diseases such as inflammatory bowel disease,but its use in functional GI disorders(FGIDs)is largely unknown although promising.In order to review the current knowledge on current and potential uses of GIUS in FGIDs,information was obtained via a structured literature search through PubMed,EMBASE and Google Scholar databases with a combination of MESH and keyword search terms:“ultrasound”,“functional GI disorders”,“irritable bowel syndrome”,“functional dyspepsia”,“intestinal ultrasound”,“point of care ultrasonography”,“transabdominal sonography”,“motility”,“faecal loading”,“constipation”.GIUS is currently used for various settings involving upper and lower GI tracts,including excluding organic diseases,evaluating physiology,guiding treatment options and building rapport with patients.GIUS can be potentially used to correlate mechanisms with symptoms,evaluate mechanisms behind treatment efficacy,and investigate further the origin of symptoms in real-time.In conclusion,GIUS is unique in its real-time,interactive and non-invasive nature,with the ability of evaluating several physiological mechanisms with one test,thus making it attractive in the evaluation and management of FGIDs.However,there are still limitations and concerns of operator dependence and lack of validation data for widespread implementation of GIUS in FGIDs.

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

Several studies indicate a significant degree of overlap between irritable bowel syndrome(IBS)and gastroesophageal reflux disease(GERD).Likewise,both functional heartburn(FH)and IBS are functional digestive disorders that may occur in the same patients.However,data establishing a solid link between FH and IBS are lacking,mainly because the clinical definition of FH has undergone substantial changes over the years.The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS.In particular,several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH(as defined by the RomeⅢcriteria)from GERD via pathophysiological investigations.Independent of these critical issues,there is preliminary evidence supporting a significantdegree of FH-IBS overlap.This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications,particularly to distinguish FH from GERD.This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

Sleep,immunity and inflammation in gastrointestinal disorders

Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.

Partially hydrolyzed guar gum in pediatric functional abdominal pain

AIM:To assess the effects of partially hydrolyzed guar gum(PHGG) diet supplement in pediatric chronic abdominal pain(CAP) and irritable bowel syndrome(IBS).METHODS:A randomized,double-blind pilot study was performed in sixty children(8-16 years) with functional bowel disorders,such as CAP or IBS,diagnosed according to Rome Ⅲ criteria.All patients underwent ultrasound,blood and stool examinations to rule out any organic disease.Patients were allocated to receive PHGG at dosage of 5 g/d(n = 30) or placebo(fruitjuice n = 30) for 4 wk.The evaluation of the efficacy of fiber supplement included IBS symptom severity score(Birmingham IBS Questionnaire),severity of abdominal pain(Wong-Baker Face Pain Rating Score) and bowel habit(Bristol Stool Scale).Symptom scores were completed at 2,4,and 8 wk.The change from baseline in the symptom severity scale at the end of treatment and at 4 wk follow-up after treatment was the primary endpoint.The secondary endpoint was to evaluate compliance to supplementation with the PHGG in the pediatric population.Differences within groups during the treatment period and follow-up were evaluated by the Wilcoxon signed-rank test.RESULTS:The results of the study were assessed considering some variables,such as frequency and intensity of symptoms with modifications of the bowel habit.Both groups were balanced for baseline characteristics and all patients completed the study.Group A(PHGG group) presented a higher level of efficacy compared to group B(control group),(43% vs 5%,P = 0.025) in reducing clinical symptoms with modification of Birmingham IBS score(median 0 ± 1 vs 4 ± 1,P = 0.025),in intensity of CAP assessed with the Wong-Baker Face Pain Rating Score and in normalization of bowel habit evaluated with the Bristol Stool Scale(40% vs 13.3%,P = 0.025).In IBS subgroups,statistical analysis shown a tendency toward normalization of bowel movements,but there was no difference in the prevalence of improvement in two bowel habit subsets.PHGG was therefore better tolerated without any adverse effects.CONCLUSION:Although the cause of pediatric functional gastrointestinal disorders is not known,the results show that complementary therapy with PHGG may have beneficial effects on symptom control.

Cow’s milk-induced gastrointestinal disorders:From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders.Cow’s milk protein allergy(CMPA)is the most common food allergy,especially in infancy and childhood,which may persist into adulthood.There are three main types of CMPA;immunoglobulin E(IgE)-mediated CMPA,non-IgEmediated CMPA,and mixed type.CMPA appears before the first birthday in almost all cases.Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis.CMPA(often non-IgE mediated)can present with symptoms of gastroesophageal reflux,eosinophilic esophagitis,hemorrhagic gastritis,food protein-induced protein-losing enteropathy,and food protein-induced enterocolitis syndrome.Most CMPAs are benign and outgrown during childhood.CMPA is not as common in adults as in children,but when present,it is usually severe with a protracted course.Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose.Lactose intolerance has four typical types:Developmental,congenital,primary,and secondary.Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults.They are also common in inflammatory bowel diseases.Milk consumption may have preventive or promoter effects on cancer development.Milk may also become a source of microbial infection in humans,causing a wide array of diseases,and may help increase the prevalence of antimicrobial resistance.This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.

Irritable bowel syndrome in children:Current knowledge, challenges and opportunities

Irritable bowel syndrome(IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their families and poses a significant burden on healthcare systems. Standard symptom-based criteria for diagnosis of pediatric IBS have changed several times during the past two decades and there are some differences in interpreting symptoms between different cultures. This has posed a problem when using them to diagnose IBS in clinical practice. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. A few potential therapeutic modalities have been tested in children and only a small number of them have shown some benefit. In addition, most of the described patho-physiological mechanisms and treatment options are based on adult studies. These have surfaced as challenges when dealing with pediatric IBS and they need to be overcome for effective management of children with IBS. Recently suggested top-down and bottom-up models help integrating reported patho-physiological mechanisms and will provide an opportunity for better understanding of the diseases process. Treatment trials targeting single treatment modalities are unlikely to have clinically meaningful therapeutic effects on IBS with multiple integrating patho-physiologies. Trials focusing on multiple combined pharmacological and non-pharmacological therapies are likely to yield more benefit. In addition to treatment, in the future, attention should be paid for possible prevention strategies for IBS.

Effectiveness of acupuncture to treat irritable bowel syndrome: A meta-analysis

AIM: To evaluate the efficacy of acupuncture for treatment of irritable bowel syndrome (IBS) through meta-analysis of randomized controlled trials.

Irritable bowel syndrome symptom severity improves equally with probiotic and placebo

AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome(IBS) symptoms and quality of life(Qo L).METHODS In this randomized triple-blind trial, adult IBS volunteerswho were recruited according to Rome Ⅲ criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score(IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk runin period, after 4 and 12 wk of intervention, and after a 4-wk washout.RESULTS A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline(VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively(P value for placebo vs combined active doses = 0.0460).CONCLUSION NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.

Consumption of spicy foods and the prevalence of irritable bowel syndrome

AIM:To explore the association between consumption of spicy foods and prevalence of irritable bowel syndrome(IBS)among Iranian adults.METHODS:In this cross-sectional study,data from4763 Iranian adult participants were used.Consumption of spicy foods was estimated using a dietary habits questionnaire that included a question on spicy foods consumption:"how frequently do you use spicy foods(pepper,curry,ginger,cinnamon and turmeric)during a week?"Participants could respond to the question by choosing one of these choices:never,1-3 times,4-6times,7-9 times,or more than 10 times per week.A modified Persian version of the RomeⅢquestionnaire was used to determine the prevalence of IBS.RESULTS:IBS was prevalent in 21.7%(18.6%of men and 24.1%of women)of the study population.After controlling for potential confounders including dietary behaviors,those consuming spicy foods≥10 times per week were 92%more likely to have IBS compared with those who never consumed spicy foods(OR=1.92;95%CI:1.23-3.01,Ptrend<0.01).The association remained significant even after taking lactose intolerance into account(OR=1.85;95%CI:1.18-2.90,Ptrend<0.01).Stratified analysis by gender revealed that the association between consumption of spicy foods and IBS was not significant in men;however,a significant association was found among women after taking potential cofounders,including meal regularity and lactose intolerance,into account.Women who consumed spicy foods≥10 times per week were two times more likely to have IBS compared with those who never consumed spicy foods(OR=2.03;95%CI:1.09-3.77,Ptrend=0.02).CONCLUSION:Consumption of spicy foods is directly associated with IBS,particularly in women.Further,prospective studies are warranted to(1)examine this association in other populations;and(2)evaluate whether dietary interventions,for example a reduction in spice consumption,would improve IBS symptoms.

Epidemiological and clinical perspectives on irritable bowel syndrome in India, Bangladesh and Malaysia: A review

Irritable bowel syndrome(IBS) is a chronic gastrointestinal disorder, common in clinic and in the community. It has a significant impact on both society and patients' quality of life. The epidemiology, clinical presentation, and management of IBS may vary in different geographical regions due to differences in diet, gastrointestinal infection, socio-cultural and psychosocial factors, religious and illness beliefs, symptom perception and reporting. Although previous reviews and consensus reports on IBS in Asia have been published, Asia is quite diverse socio-demographically. In this context, India, Bangladesh and Malaysia share some similarities, including:(1) large proportion of the population living in rural areas;(2) rapid development and associated lifestyle changes in urban areas; and(3) dietary, cultural and religious practices. The present review explores the clinical and epidemiological data on IBS from these three major nations in South and South-East Asia. In-depth review of the literature revealed important differences between IBS in the East, as revealed by studies from these three countries, and the West; these include a predominantly rural profile, differences in bowel habit and symptom profile, raising concern with regards to diagnostic criteria and subtyping of IBS, higher dietary fiber consumption, frequent lactose malabsorption, parasitosis, and possible overlap between post-infectious IBS and tropical sprue. Moreover, the current perception on difference in prevalence of the disorder in these countries, as compared to the West, might be related to variation in survey methods.

Attention deficit hyperactivity disorder and gastrointestinal morbidity in a large cohort of young adults

BACKGROUND Although the association of attention deficit hyperactivity disorder(ADHD)with psychiatric disorders is well known,its association with somatic diseases is unclear.Only few studies have investigated the gastrointestinal(GI)morbidity in adult patients with ADHD.AIM To measure gastrointestinal comorbidity and its burden on healthcare in young adults with ADHD.METHODS The cohort included subjects aged 17-35 years recruited to the Israel Defense Forces in 2007-2013,33380 with ADHD and 355652 without(controls).The groups were compared for functional and inflammatory conditions of the gastrointestinal tract and clinic and specialist visits for gastrointestinal symptoms/disease during service(to 2016).Findings were analyzed by generalized linear models adjusted for background variables.RESULTS Compared to controls,the ADHD group had more diagnoses of functional gastrointestinal disorders(referred to as FGID),namely,dyspepsia[odds ratio(OR):1.48,95%confidence interval(CI):1.40-1.57,P<0.001],chronic constipation(OR:1.64,95%CI:1.48-1.81,P<0.001),and irritable bowel syndrome(OR:1.67,95%CI:1.56-1.80,P<0.001)but not of organic disorders(inflammatory bowel disease,celiac disease).They had more frequent primary care visits for gastrointestinal symptoms[rate ratio(RR):1.25,95%CI:1.24-1.26,P<0.001]and referrals to gastrointestinal specialists(RR:1.96,95%CI:1.88-2.03,P<0.001)and more episodes of recurrent gastrointestinal symptoms(RR:1.29,95%CI:1.21-1.38,P<0.001).Methylphenidate use increased the risk of dyspepsia(OR:1.49,95%CI:1.28-1.73,P<0.001)and constipation(OR:1.42,95%CI:1.09-1.84,P=0.009).CONCLUSION ADHD in young adults is associated with an excess of FGID and increased use of related health services.Research is needed to determine if an integrative approach treating both conditions will benefit these patients and cut costs.